Typhoid fever is a major cause of illness and mortality in low- and middle-income settings. We investigated the association of typhoid fever and rainfall in Blantyre, Malawi, where multi-drug-resistant typhoid has been transmitting since 2011. Peak rainfall preceded the peak in typhoid fever by approximately 15 weeks [95% confidence interval (CI) 13.3, 17.7], indicating no direct biological link. A quasi-Poisson generalised linear modelling framework was used to explore the relationship between rainfall and typhoid incidence at biologically plausible lags of 1–4 weeks. We found a protective effect of rainfall anomalies on typhoid fever, at a two-week lag (P = 0.006), where a 10 mm lower-than-expected rainfall anomaly was associated with up to a 16% reduction in cases (95% CI 7.6, 26.5). Extreme flooding events may cleanse the environment of S. Typhi, while unusually low rainfall may reduce exposure from sewage overflow. These results add to evidence that rainfall anomalies may play a role in the transmission of enteric pathogens, and can help direct future water and sanitation intervention strategies for the control of typhoid fever.